37 to 0.52) and with oim data having lower stiffness despite having a higher mineral volume fraction. Oyen et al. [8] have also observed such a wide range of elasticity values despite equivalent mineral volume fractions and concluded that no single

Afatinib in vitro relation could be found to estimate the bone elasticity from its mineral composition. This large variation of bone matrix elasticity at fixed mineral composition can be explained by introducing more finely defined ultra-structural features into the composite model. In the context of a stiff continuous (or partially continuous) mineral matrix laid upon a collagen scaffold, finite element studies of the discrete ultra-structure have shown that the connectivity of the crystal particles forming the mineral phase strongly influence the bone composite modulus (at a constant mineral volume fraction) [50] and [51]. This crystal connectivity is related to the crystal shape (aspect ratio), orientation and arrangement, which is most likely dictated by the organization and quality of the collagen network. Here we focus on the compressive elastic properties of the matrix (nanoindentation), which are primarily related to the mineral phase. We anticipate that the altered collagen structure plays an important role in the plastic behavior of the matrix. Thus, the short, poorly

arranged and tightly packed apatite crystals seen in our TEM images of oim bone is a consequence of the collagen alterations and may explain why oim modulus values are below wild type despite the increased mineralization. The composite framework allows Daporinad us to examine how changes in the ultra-structure (protein/mineral structure) can alter the modulus independent of mineral fraction. We observed no correlation between the bone mineralization and stiffness at the microscopic scale either in the oim or in the wild type mice. This has important implications in bone pathologies and the therapeutic strategies developed

to counter their effects. Therapies that promote apposition and accumulation of hyper-mineralized Nintedanib (BIBF 1120) bone tissue, may have the limitation of accumulating bone with poor structural and mechanical properties with possible long term negative effects [52] and [53]. As available clinical radiographic techniques are limited in their measure of bone “quality”, it should be of great interest to develop and validate testing techniques that allow the mechanical investigation of tissue and matrix properties in the clinic. This research was funded by the British Birth Defect Foundation, the Genesis Research Trust and by the European Union FP7 project number 257182 (CNTBBB). “
“A relationship between iron and FGF23 metabolic pathways has been proposed [1], [2], [3] and [4]. A study on a random selection of stored clinical biochemistry samples has indicated an inverse relationship between ferritin and FGF23 concentrations [3].